Who and where is the renal baroreceptor?: the connexin hypothesis

Gap junctions are emerging as a fundamental mechanism for the control of renin synthesis and release. Connexin40 is prominent in juxtaglomerular cells. When missing, it results in hyperreninemia and hypertension. Schweda et al. offer exciting data demonstrating that connexin45, a connexin with different biophysical properties, can replace connexin40 functions related to the control of renin

Risk Classification of Bladder Cancer by Gene Expression and Molecular Subtype

This study evaluated a panel including the molecular taxonomy subtype and the expression of 27 genes as a diagnostic tool to stratify bladder cancer patients at risk of aggressive behavior, using a well-characterized series of non-muscle invasive bladder cancer (NMIBC) as well as muscle-invasive bladder cancer (MIBC). The study was conducted using the novel NanoString nCounter gene expression analysis. This technology allowed us to identify the molecular subtype and to analyze the gene expression of 27 bladder-cancer-related genes selected through a recent literature search. The differential gene expression was correlated with clinicopathological variables, such as the molecular subtypes (luminal, basal, null/double negative), histological subtype (conventional urothelial carcinoma, or carcinoma with variant histology), clinical subtype (NMIBC and MIBC), tumor stage category (Ta, T1, and T2–4), tumor grade, PD-L1 expression (high vs. low expression), and clinical risk categories (low, intermediate, high and very high). The multivariate analysis of the 19 genes significant for cancer-specific survival in our cohort study series identified TP53 (p = 0.0001), CCND1 (p = 0.0001), MKI67 (p < 0.0001), and molecular subtype (p = 0.005) as independent predictors. A scoring system based on the molecular subtype and the gene expression signature of TP53, CCND1, or MKI67 was used for risk assessment. A score ranging from 0 (best prognosis) to 7 (worst prognosis) was obtained and used to stratify our patients into two (low [score 0–2] vs. high [score 3–7], model A) or three (low [score 0–2] vs. intermediate [score 3–4] vs. high [score 5–7], model B) risk categories with different survival characteristics. Mean cancer-specific survival was longer (122 + 2.7 months) in low-risk than intermediate-risk (79.4 + 9.4 months) or high-risk (6.2 + 0.9 months) categories (p < 0.0001; model A); and was longer (122 + 2.7 months) in low-risk than high-risk (58 + 8.3 months) (p < 0.0001; model B). In conclusion, the molecular risk assessment model, as reported here, might be used better to select the appropriate management for patients with bladder cancer

Improving graph-based detection of singular events for photochemical smog agents

Recently, a set of graph-based tools have been introduced for the identification of singular events of O3, NO2 and temperature time series, as well as description of their dynamics. These are based on the use of the Visibility Graphs (VG). In this work, an improvement of the original approach is proposed, being called Upside-Down Visibility Graph (UDVG). It adds the possibility of investigating the singular lowest episodes, instead of the highest. Results confirm the applicability of the new method for describing the multifractal nature of the underlying O3, NO2, and temperature. Asymmetries in the NO2 degree distribution are observed, possibly due to the interaction with different chemicals. Furthermore, a comparison of VG and UDVG has been performed and the outcomes show that they describe opposite subsets of the time series (low and high values) as expected. The combination of the results from the two networks is proposed and evaluated, with the aim of obtaining all the information at once. It turns out to be a more complete tool for singularity detection in photochemical time series, which could be a valuable asset for future research.Comment: 35 pages, 7 figure